Posted 18 April 2011
A principle in scientific research and science writing is to always go back to the primary source documents as far as possible. Ideally one would want to be able to double-check actual data from studies — but most of the time we have to be content with the published versions of the research. Here’s an example of how not going back to the original publication, and relying on a secondary source (a university newspaper) led to a mistake which has then been used in making false claims for a product.
Solal have been marketing an “anti-aging pill” which they claim/infer, among other, can slow down human ageing and extend the human lifespan.
Their website — which is no longer accessible since this blog was first published (http://www.solaltech.com/antiaging.htm) showed the graphic above which asks “Is an anti-aging pill possible?” Text that implies this is factual is produced below the graphic followed in small print with a series of references that look at face value to be very credible. (Solal still markets this product here)
Believe this so far?
In large print, Professor David Sinclair, “Resveratrol researcher, Harvard Medical School”, is quoted as stating: “Resveratrol extends the life of every species it’s given to. We’re 50 years ahead of where I thought we would be 10 years ago.”
The references which are not easy to read are provided below as they appear in the graphic. These references (except 11 which is a book) were obtained and analysed to see if they were used in context and to verify the claims made in the graphic on the website.
1. Journal of nutrition 2002 Feb;132(2):257-60.
2.Hall SS.: Longevity research. In vino vitalis? Compounds activate life-extending genes.: Science 2003 Aug 29;301(5637):1165
3.Cromie, WJ; Protein extends life; Harvard University Gazette; 2004 July; II
4.Shi J, Yu J, Pohorty JE, Kakuda Y.; Polyphenolics in grape seeds – biochemistry and functionality; Journal of Medicinal Food. 2003 Winter;6(4):291-9. Review.
5.Delmas D, Jannin B, Latruffe N.; Resveratrol: preventing properties against vascular alterations and ageing.: Mol Nutr Food Res. 2005 May;49(5):377-95.
6.Journal of Hypertension 2000 Dec;18:1833-40.
7.International Immunopharmacology 2005 May;5(5):849-56
8.Ann NY Academy Sciences 2003 May;993:276-86.
9.de la Lastra CA, Villegas I.; Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications.; Mol Nutr Food Res. 2005 May;49(5):405-30.
10.International Cancer Journal. 2005 June 10;115(2):196-201.
11.Clouatre, Dallas. All about grape seed extract, Avery Publishing Group. Garden City Park, New York, USA. 1998:56
The text continues: “In June 2004, researchers at Harvard Medical School discovered that a safe protein molecule known as Resveratrol, extracted from (grape) vine leaves, activates a gene which slows down the rate at which cells age and can extend the lifespan of human cells by 14-23%.” (I added the underlining)
Each of these three underlined words or phrases is associated with the references above. The first, a 2002 reference  (published a whole two years before the Harvard researchers made their “discovery”!) tells us that resveratrol is not harmful when given to rats for 28 days. This clearly does not necessarily mean resveratrol (or this product) is safe for humans.
The second, a 2003 reference  (a whole year before the Harvard researchers made their “discovery”) does describe the activation of a gene which affects cellular aging — but these are yeast cells. The article also mentions that “some protection to cultured human cells exposed to radiation” is offered by several naturally occurring small molecules. Although “Science” is a reputable journal — this information comes from an unreferenced “news of the week” report! One cannot extrapolate from yeast cells or damaged cultured human cells in a laboratory to actual real living human beings.
The third reference comes from the Harvard University Gazette in 2004 . This is a university newspaper — not a peer-reviewed journal — and it does not state that resveratrol can extend the life of human cells by 14-23%. The statement seems to be a complete fabrication. If you read the original research published as a letter co-authored by Professor Sinclair in the highly prestigious journal “Nature”, you will discover that the research was not done in human cells but in worms and fruit flies. The worms’ lifespan was extended by 14%, whereas the fruit flies’ lifespan was extended by 29% on resveratrol, not 23%! The fruit flies’ lifespan was extended by 23% with “fisetin” — another compound that was being tested at the same time. So the Harvard Gazette writer’s mistake seems to have been simply echoed by Solal, but with the little “addition” of extending the lifespan of “human cells.” Oops!
The label for the “Anti-Aging Pill” is still accessible on the Solal website at: http://www.solaltech.com/products/nutriceuticals/anti_aging_pill/ANTI%20AGING%20PILL.swf . On it is a repeat of the erroneous statement that
“[i]n 2002, Harvard University Medical School showed that resveratrol extends the life-span of human cells by up to 23%.”
NOT ONLY WAS THIS RESEARCH NOT IN 2002, IT WAS NOT IN HUMAN CELLS BUT IN FRUIT FLIES, AND IT WAS NOT RESVERATROL BUT FISETIN. (Oops, oops, oops)
The label for the Resveratrol Extra Strength refers to : “Nobel prize winning research into Resveratrol has proven that it is one of the most important anti-aging and disease preventive nutrients recently discovered” [Comment — but not in humans!] and “[I]n 2002, Harvard Medical School showed than (sic) Resveratrol has life-extension potential, by slowing down the rate at which DNA ages.” http://www.solaltech.com/newonepagers/RESVERATROL%20-EXTRA_STRENGTH.swf . Several other unproven claims for resveratrol are also made on the label.
Apologies for any repetition in the next sections. It makes similar points for both these products in different ways.
|A. What should you ask the company?|
(I certainly would!)
1. Has Solal ever conducted any studies on these formulations?
NO, there is no evidence that Solal has conducted even a single study in humans to confirm whether these combinations have any effectiveness or whether they are safe. (Yes, you the consumer are the unwitting guinea pig which is a contravention of the Constitution of South Africa!)
2. Does the evidence show that resveratrol can really extend the lifespan of human cells by 14-23%?
No, this is a blatant misrepresentation of the truth, and in fact, misquotes the Harvard study. The 14% refers to worms not human cells and the 23% refers to fruit flies (receiving fisetin not resveratrol), not human cells. The misinformation seems to have come from a mistake in the university newspaper about the findings but then somehow applying it to human cells. See above and point B. a. below for more details.
3. Is there sufficient evidence to back up the other claims being made for these products?
No, similar to point 2 above, the evidence is mostly derived from cells in lab dishes and/or rat studies. Some clinical studies have been conducted on Grape seed extract (on its own) for specific conditions which do not include the anti-aging claims. See specific details above.
4. Has Solal accurately conveyed Professor David Sinclair’s most recent point of view?
No, Professor David Sinclair statement has not even been quoted ‘correctly’ – it is out of context are therefore inappropriate and incorrect! See point B. b. below.
5. Has the safety of this product been tested on humans?
No, this has been “guessed”. There is no evidence that the individual ingredients or this mixture have ever been tested in short or long term studies on humans. Furthermore, one does not know for sure whether the ingredients would be synergistic (enhance each other) or would be antagonistic (oppose each other). See point B. c. below
6. Is there evidence that these products may be unsafe for human consumption?
Yes, Although no studies have been conducted in humans, in animal models resveratrol has been shown to have a dual action – at one dose it may have efficacy and be safe, at another dose it promotes cancer. (This is sometimes called the hormetic dose response.) Of course this may only be relevant in animal models, but these models warn that the same may apply to humans. What are the equivalent doses in humans? We don’t know, and certainly Solal doesn’t know! It could be the doses that these products contain – but there is no proof from human studies that they are.
7. Does a patent signify that the product has efficacy?
No, proof that the product works is not required before a patent is obtained (and as it is “pending” it has in this case not even been been granted yet). It is interesting that the information provided on the webpage about the patent pending product — the Anti-Aging Pill is so blatantly erroneous.
|B. Further details and scientific evidence|
|a.)||Does recent evidence confirm that anti-aging in humans with these compounds is possible?|
No. To date all the evidence is derived from studying cells in dishes in the laboratory, or from worm, fruit fly, rat or other animal studies. No conclusive human studies have been published.
Solal quoted Professor David Sinclair: “Resveratrol extends the life of every species it’s given to. We’re 50 years ahead of where I thought we would be 10 years ago”
Solal also quoted: “In June 2004, researchers at Harvard Medical School . . . showed how . . . in experimental models on yeasts, fruit flies and human cells resveratrol increased lifespan by 14-23% ” (NB: The research quoted was done on worms (14%) and fruit flies (23%)). The original research did not use human cells at all!
A simple Google search leads one to the source of these statements, The Harvard University Gazette which states: “This year, he [Sinclair] fed a closely related protein to tiny worms and fruit flies. The worms lived as much as 14 percent longer, the flies as much as 23 percent. If it works in humans, that would extend our roughly 83-year lives to about 95 or 102”, and, “[w]e have something that extends the life of every species it’s given to,” Sinclair enthuses. “We’re 50 years ahead of where I thought we would be 10 years ago.” But the article goes on to say “The protein works on human cells growing in a test tube, but will it work on baby boomers trying to live the good life longer? ‘It’s pure speculation at this point, but we now have the first molecule that extends life in species, from fungi to flies’ [he said]” (Emphasis added) How come his point about speculation wasn’t quoted?
But as already pointed out, even the Harvard University Gazette got it wrong! The fruit flies lived 23% longer when given “fisetin” not resveratrol. The resveratrol fed fruit flies lived 29% longer. This shows how important it is to access the original published research and not just a news report (even that of a reputable university).
It would seem that Solal most likely did not access the original article in the journal Nature about the effects of resveratrol on worms and fruit flies respectively and ended up quoting the incorrect figures for fruit flies. Not that this really makes a difference to whether or not it has an effect in humans — that is still undetermined, despite Solal’s claims.
The real concern is that once again Solal have made a mistake in its interpretation of scientific data. See also the article on this website on distorting evidence.
Solal’s most recent evidence on their website is from 2005. In 2011, that’s 6 years ago — a long time in scientific circles.
More recent reviews published in credible medical journals point out that we are no closer to this answer:
|(i).||“A plethora of laboratory investigations has provided evidence for the multi-faceted properties of resveratrol and suggests that resveratrol may target ageing and obesity related chronic disease by regulating inflammation and oxidative stress. A number of obstacles stand in the path to clinical usage however, not least the lack of clinical evidence to date, and the myriad of doses and formulations available. Further, data on the effects of resveratrol consumption in a capsule versus food form is conflicting, and there are uncertain effects of long-term dosing.” [Emphasis added] Chachay VS, Kirkpatrick CM, Hickman IJ, Ferguson M, Prins JB, Martin JH. Resveratrol – pills to replace a healthy diet? Br J Clin Pharmacol. 2011 Mar 16. doi: 10.1111/j.1365-2125.2011.03966.x. [Epub ahead of print] |
|(ii).||“An expanding body of preclinical evidence suggests resveratrol has the potential to impact a variety of human diseases. To translate encouraging experimental findings into human benefits, information is first needed on the safety, pharmacokinetics, pharmacodynamics, and, ultimately, clinical efficacy of resveratrol. [However,] [p]ublished clinical trials have largely focused on characterizing the pharmacokinetics and metabolism of resveratrol [rather than clinical efficacy]. Recent studies have also evaluated safety and potential mechanisms of activity following multiple dosing, and have found resveratrol to be safe and reasonably well-tolerated at doses of up to 5 g/day. However, the occurrence of mild to moderate side effects is likely to limit the doses employed in future trials to significantly less than this amount. This review describes the available clinical data, outlines how it supports the continuing development of resveratrol, and suggests what additional information is needed to increase the chances of success in future clinical trials.” [Emphasis added] (In other words, there is no sufficient evidence yet!).|
Patel KR, Scott E, Brown VA, Gescher AJ, Steward WP, Brown K. Clinical trials of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215:161-9. doi: 10.1111/j.1749-6632.2010.05853.x.
Comment: This article summarises 16 studies in 338 humans (assuming that none of the articles covered research that had the same participants). Despite this research there is no evidence for the clinical use of resveratrol.
|(iii)||The highly respected Medical Letter in 2009 concluded: “Resveratrol appears to produce some of the same effects as calorie-restricted diets that have reduced the incidence of age-related diseases in animals. Whether it has any benefit in humans remains to be established.” [Emphasis added] Resveratrol. The Medical Letter on Drugs and Therapeutics, 2009 Sep 21;51(1321):74-5. |
|(iv)||NMCD states for resveratrol:|
Effectiveness: There is insufficient reliable information available about the effectiveness of resveratrol [for atherosclerosis, lowering cholesterol levels, increasing HDL cholesterol levels, and preventing cancer.] No mention of anti-aging effects.
NMCD on effectiveness of Grape seed extract:
Nothing listed for anti-aging effects!
|b.)||Has Solal been accurate regarding Professor David Sinclair’s position?|
Although Professor David Sinclair first statement may have been quoted correctly, the rest of the claims are out of context, extrapolated from theory or animal models and are therefore incorrect.
A full two years after Professor David Sinclair’s “quote” in Solal’s advert, Prof. Sinclair himself and Prof AL Komaroff, another world authority on resveratrol, wrote in a Newsweek article (“Can we slow aging?” 2006 Dec 11;148(24):80, 82, 84), the following:
Clearly even Professor Sinclair himself does not endorse the use of resveratrol in humans.
|c.)||Is this product safe as claimed by Solal?|
There is no proof that this product is safe:
|(i)||There is no evidence that Solal have EVER conducted any short or long term studies to confirm the safety of this product.|
|(ii)||Natural Medicines Comprehensive Database review states “[T]here is insufficient reliable information available about the safety of resveratrol when used in supplemental doses in amounts greater than those found in foods.”|
|(iii)||Three recent reviews highlights the potential risk of taking resveratrol: “At higher doses, resveratrol depresses cardiac function, elevates levels of apoptotic protein expressions, results in an unstable redox environment, increases myocardial infarct size and number of apoptotic cells. At high dose, resveratrol not only hinders tumor growth but also inhibits the synthesis of RNA, DNA and protein, causes structural chromosome aberrations, chromatin breaks, chromatin exchanges, weak aneuploidy, higher S-phase arrest, blocks cell proliferation, decreases wound healing, endothelial cell growth by fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor, and angiogenesis in healthy tissue cells leading to cell death. Thus, at lower dose, resveratrol can [possibly] be very useful in maintaining the human health whereas at higher dose, resveratrol has pro-apoptotic actions on healthy cells, [i.e. healthy cells’ lifespan is ended] but can kill tumor cells.” [emphasis added] Mukherjee S, Dudley JI, Das DK. Dose-dependency of resveratrol in providing health benefits. Dose Response. 2010 Mar 18;8(4):478-500.|
Comment: Although this is not based on human data, it is an advance on the information provided by Solal.
“Resveratrol induces hormetic dose responses [a biphasic dose-response model characterized by opposite effects at low and high doses] in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. These responses were reported for numerous human tumor cell lines affecting breast, prostate, colon, lung, uterine and leukemia. In such cases, low concentrations of resveratrol enhanced tumor cell proliferation whereas higher concentrations were inhibitory.” “Hormetic effects were also reported in animal models for cardiovascular induced injury, gastric lesions, ischemic stroke, Alzheimer’s disease and osteoporosis. In these cases, there was often a protective effect at low doses but an adverse effect at higher doses, exacerbating the disease process/incidence. This analysis indicates that many effects induced by resveratrol are dependent on dose and that opposite effects occur at low and high doses, being indicative of a hormetic dose response. Despite consistent occurrence of hormetic dose responses of resveratrol in a wide range of biomedical models, epidemiologic and clinical trials are needed to assess the nature of its dose-response in humans.” [emphasis added]
Calabrese EJ, Mattson MP, Calabrese V. Resveratrol commonly displays hormesis: occurrence and biomedical significance. Hum Exp Toxicol. 2010 Dec;29(12):980-1015.
Comment: Although this is not based on human data, it is an advance on the information provided by Solal.
“The effects of resveratrol represent a ‘two-edged sword’ in that it has contrasting effects at low and high doses in healthy and cancerogenous cells. What demarcates a low and a high dose needs to be clarified. Concentrations tested in cell cultures, moreover, may not be relevant to whole organisms. And data from animal models need not apply to humans. Co-morbidities should also be considered. More research is needed to understand the action of resveratrol on all cell types and conditions, and the optimum therapeutic concentration that applies to each of these. Future research needs to determine the dynamics of the effects of resveratrol in different subcellular compartments and the interactions of these. In addition, the interactions between resveratrol, environmental factors, other compounds and medications, diseases and the genetic background of the individual will need to be appreciated in order to gain a complete understanding of the hormetic response of resveratrol. [emphasis added]
Marques FZ, Morris BJ. Commentary on Resveratrol and Hormesis: Resveratrol—a hormetic marvel in waiting? Hum Exp Toxicol. 2010 Dec;29(12):1026-8.
Comment: This is also not based on human data, but is an advance on the information provided by Solal.
CONCLUSION: Is an anti-aging pill possible? Maybe. Do Solal’s “Anti-Aging Pill” and “Resveratrol Extra Strength with Grape Seed Extract” have anti-aging effects in humans? No. There is no evidence that they have any anti-aging effects. In fact the evidence provided by Solal is quite insufficient and inappropriate to ensure that taking these products will add years to your life or that the quality of your life and health as you age, will be improved. There’s also no evidence that these products will help to prevent any of the debilitating diseases that develop with age. But to crown it all, the interpretation of the evidence provided is faulty, and as already shown — a part of it may even be fabricated. In fact, I can say with certainty that in taking these products, not only will you continue to get older, but you will also be poorer.